The C1q and collectin binding site within C1q receptor (cell surface calreticulin).
C1q receptor (C1qR/collectin receptor/cC1qR) has an almost complete amino acid sequence identity with calreticulin (CRT). C1qR/CRT is located on the surface of many cell types. Binding of C1q to C1q receptor elicits a range of immunological responses. C1qR also interacts with the collectins SP-A, MBL, CL43 and conglutinin via a cluster of charged residues on the collagen tails of the ligands. In order to localise C1q and collectin binding activity within C1qR/CRT, recombinant C1qR/CRT domains [N (residues 18-196), P (197-308) and C (309-417)] were produced. Both the N- and P-domains bound to C1q, demonstrating that the binding site spans the intersection of these domains. Amino acid alignment analysis identified a putative CUB module within this region. This S-domain (residues 160-283) was expressed and showed concentration-dependent binding to immobilised C1q, demonstrating that it contains the C1q binding site. Competitive inhibition studies of the S-domain-C1q interaction revealed that the S-domain binds to C1q collagen tails and to the collectin proteins, SP-A, MBL, CL43 and conglutinin. The C1q and collection binding site on C1qR/CRT has therefore been localised to the S-domain.
Stuart
G R
GR
Department of Biochemistry, University of Oxford, UK.
Lynch
N J
NJ
Day
A J
AJ
Schwaeble
W J
WJ
Sim
R B
RB
D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D037282:Calreticulin; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D002460:Cell Line; D003094:Collagen / Q000737:chemistry; D037222:Collectins; D015922:Complement C1q / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D018960:Hyaluronan Receptors; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D011951:Receptors, Complement / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment
C087299:C1QBP protein, human; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002352:Carrier Proteins; D037222:Collectins; D018960:Hyaluronan Receptors; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; C032402:complement 1q receptor; D015922:Complement C1q; D003094:Collagen